Full-genome deep sequencing and phylogenetic analysis of novel human betacoronavirus

An analysis of the sequence of the first UK case including deep sequencing of within-patient diversity can be found here:

Cotten M, Lam TT, Watson SJ, Palser AL, Petrova V, Grant P, Pybus OG, Rambaut A, Guan Y, Pillay D, Kellam P, Nastouli E (2013) Full-genome deep sequencing and phylogenetic analysis of novel human betacoronavirus. Emerg Infect Dis. Volume 19, May 2013 http://dx.doi.org/10.3201/eid1905.130057External Web Site Icon

Abstract. A novel betacoronavirus associated with lethal respiratory and renal complications was recently identified in patients from several countries in the Middle East. We report the deep genome sequencing of the virus directly from a patient’s sputum sample. Our high-throughput sequencing yielded a substantial depth of genome sequence assembly and showed the minority viral variants in the specimen. Detailed phylogenetic analysis of the virus genome (England/Qatar/2012) revealed its close relationship to European bat coronaviruses circulating among the bat species of the Vespertilionidae family. Molecular clock analysis showed that the 2 human infections of this betacoronavirus in June 2012 (EMC/2012) and September 2012 (England/Qatar/2012) share a common virus ancestor most likely considerably before early 2012, suggesting the human diversity is the result of multiple zoonotic events.


Figure 3. Phylogenetic analyses of coronaviruses. A–F) Maximum-likelihood phylogenies of combined and each individual open reading frame (ORF), including ORF 1ab, S, E, M, and N. Previously defined viral lineages (group 1, 2a, 2b, 2c, 2d, 3, and 4) are highlighted by color blocks and described in (A). G) Phylogenetic analyses on the partial RNA-dependent RNA polymerase sequence region (396 bp) of coronaviruses (CoVs). Partial gene sequences from other CoVs that are closely related to the novel human betaCoVs are included and marked with asterisks. Bootstrap analysis of 1,000 replicates was performed for each phylogeny. The novel human betaCoVs studied here are shown in red. Scale bar indicates nucleotide substitutions per site.

The alignment for the partial RdRp gene region used to create panel G in the above figure is available here: partialRdRp.fas